While colchicine has been utilized for centuries and more recently as a pharmacological tool, its mechanism of action remains obscure. It is proposed that many of the actions of this agent result from reversible interaction with biological nucleophiles. Methods have been proposed for both chemical and enzymatic evaluation of such an interaction based on other alkylating antitumor agents. Because of toxicity exhibited by colchicine in anticancer therapy, interest has recently been focused on phenolic analogs exhibiting decreased toxicity while maintaining equipotency therapeutically. However, few of these derivatives have been examined because of a lack of selective and mild procedures for O-demethylation. Newer chemical methods for this type reaction will be examined based on their mild reaction conditions and demonstrated regiospecificity with alkaloids. In addition, microbial transformations will be examined for regiospecific O-dealkylation of colchicine. Ester and carbamate prodrugs of phenolic colchicine derivatives will be prepared for antitumor evaluation. The in vivo and in vitro hydrolysis and metabolism of these prodrugs will be examined to correlate these results with observed antitumor effects.